Dexamethasone enhances accumulation of cholesteryl esters by human
macrophages.
Cheng, Wanli, Kara V. Kvilekval, and Nada A. Abumrad.
Departments of Surgery and of Physiology and Biophysics, State
University of New York at Stony Brook, Stony Brook NY, 11794
APStracts 2:0099E, 1995.
The effects of dexamethasone on lipid accumulation by human monocyte
-derived macrophages were investigated. Preincubation of macrophages
with dexamethasone for a period of 16-20 hours resulted in a
reproducible increase (3.5 fold) in the incorporation of oleate into
cholesteryl esters. The effect was specific since no alterations were
observed in oleate incorporation into triglycerides or phospholipids.
Measurement of cellular cholesteryl esters indicated a fourfold
increase after preincubation with dexamethasone. This increase was
mediated by opposite effects on synthesis and breakdown of these
lipids. Dexamethasone produced a 60% increase in activity of the
enzyme acyl-CoA-cholesterol acyl transferase, ACAT, active in
synthesis of cholesteryl esters, and a 40% decrease in that of
neutral cholesteryl esterase, NCE, active in cholesteryl ester
breakdown. The increased ACAT activity appeared to reflect increased
mRNA for the enzyme. The effects of dexamethasone on cholesteryl
ester accumulation by macrophages reached statistical significance at
a concentration of 100 nM. They were dose-dependent and saturation
was observed at around 1 [mu]M. The effects were significant at low
concentrations of cholesterol in the medium. At high medium
cholesterol, there was a large cholesterol-induced increase in ACAT
activity that obscured most of the effect of dexamethasone. In
general, the data suggest that high glucocorticoid levels enhance
lipid accumulation by macrophages and thus would have an atherogenic
action that is independent of serum cholesterol.
Received 12 January 1995; accepted in final form 26 April 1995.
APS Manuscript Number E9-5.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 9 May 1995.